Metformin toxicity

Metformin, a blood-glucose-lowering drug widely used for treatment of type 2 diabetes, is associated with risk of potentially fatal metabolic (lactic) acidosis. This can occur not only following overdose but also at therapeutic dose in patients with pre-existing renal or liver disease.

Results of arterial blood gas analysis reflect metabolic acidosis (reduced blood pH, reduced bicarbonate compensatory increase in pCO₂) and increased plasma lactate. Is it possible, as might be intuitively expected, to predict survival in such cases from the severity of the acidosis and/or severity of the hyperlactatemia? That is the question addressed by a recent study. 

Investigators conducted a systematic review of the literature and identified 22 well-documented case histories of metformin overdose, five of which had a fatal outcome. For each of these cases, investigators abstracted lowest (nadir) pH, highest (peak) plasma lactate concentration and highest (peak) plasma metformin concentration. 

The median nadir pH among non-survivors was 6.71 (interquartile IQ range 6.71-6.73), this compared with median pH 7.30 (IQ range 7.22-7.36) for survivors. The median peak plasma lactate among non-survivors was 35 mmol/L (IQ range 33.3-39.0) and among survivors 10.8 mmol/L (IQ range 4.2-12.9). 

Results allowed the conclusion that patients who died following metformin overdose had much lower nadir blood pH and much higher peak plasma lactate concentration than those who survived. No patients with pH > 6.9 and plasma lactate < 25 mmol/L died. Intuition confirmed.